Determining Male Fertility
According to recent studies, male infertility (e.g. defective spermatogenesis or testicular obstruction) is responsible almost 40% of the time that a couple is unable to conceive a child. In addition, use of male contraceptives is on the rise. According to current estimates, more than 500,000 vasectomies are performed in the U.S. each year and about 10,000,000 are performed worldwide. In addition to vasectomies, a variety of oral contraceptives for use by males are in development. Although male contraceptives decrease the probability that a fertile male will initiate a pregnancy, no male contraceptive is 100% effective. Further, most male contraceptives require a certain period of time in which to take effect.
For a semen sample to be considered fertile according to standards set by the World Health Organization (WHO), at least two 1.5-5.0 milliliter ejaculate volumes obtained from a male must contain a sperm density of greater than 20 million spermatozoa/mL and/or a percent motility of 60% with a forward progression greater than 2 (on a 1-4 scale). In addition, the semen samples should show no evidence of sperm agglutination, leukocytospermia (pyospermia) or hyperviscosity (Sigman, M., et al., Evaluation of the non-fertile male. In: Lipschultz, L I and S S Howards eds. Infertility in the Male, 2nd ed. Chicago: Mosby-Year Book, 1991; p.184). A leukocyte count in semen that is greater than 1 million/ml is diagnostic by WHO criteria of leukocytospermia, a condition that is frequently associated with genitourinary infection, antisperm antibodies and male infertility.
By convention, male infertility is diagnosed based on low sperm motility and/or count. However, motility analyses can produce false negatives, since fertile sperm may appear non-motile due to damage sustained during processing. With regard to sperm count, 20 million spermatozoa/mL or greater is generally considered to be in the fertile range. However, non-motile, non-fertile sperm can be included in the count. Sperm count and motility are typically assessed using commercially available instruments, such as light microscopes and computerized videoanalysis systems.
U.S. Pat. No. 5,068,089 describes a home kit for testing fertility of human sperm based on ability of the sperm to reduce a dye. The extent of reduction (displayed calorimetrically), is said to be indicative of sperm fertilizing ability. However, this test is time consuming, requires incubation at a temperature above room temperature and does not distinguish between reduction due to sperm cells or other cells, which may be present in a semen sample.
U.S. Pat. No. 5,219,729 describes a laboratory assay for determining the fertilizing ability of sperm based on the affinity of binding to an oocyte zona pellucida fragment. The tighter the binding, the greater the fertilizing ability of the sperm sample. However, this assay requires freshly prepared oocyte fragments and at least four hour's time during which the sperm must be kept in contact with the oocyte fragment.
U.S. Pat. No. 5,434,057 describes assays and kits for determining male fertility based on the detection of fumarase activity. However, since fumarase is ubiquitously present in cells including cells that may be present in a sperm sample (epithelial, leukocyte and bacterial or fungal), whether fumarase activity is an accurate indicator of sperm count and motility, as claimed in the patent, is dubious.
A simple, rapid and accurate assay for determining the fertility of a sperm sample in a reference laboratory, doctor's office or at home is needed.